Principle Investigator/Program Director: Yoshino, TEimothy P. 0 take an integrated cellular, biochemical and molecular approach to evaluate the role of hemocyte pattern The primary objective of the current research program is to define and characterize the molecular basis for schistosome-specific CHOs. The central hypothesis to be addressed is that parasite CHOs represent the recognition receptors, emphasizing CHO-reactive lectins, in immune recognition of and reactivity to expressed carbohydrates (CHO5) and hemocyte immune function. As a result, the current research plan will Information gained over the last grant period strengthens a critical, but complex, nexus between larval- of the human blood fluke Schistosoma mansaril, causative agent of hepatosplenic schistosomiasis. innate resistance and susceptibility of inbred strains of the snail Biomphalaria glabrat.;9a to infection by larvae 3N. [unreadable]-L) together initial hemocyte-CHO interaction and expression of hemocyte effector function (ROS response). In to early developing schistosomes, this work will contribute to a greater understanding of the mechanisms of primary pathogen-associated molecular patterns (PAMPs) responsible for hemocyte immune recognition, but innate immune recognition and pathogen anti-immune responses that may well lead to the development of addition to providing important insights into the role of schistosome CHOs in regulating hemocyte responses anticipated that research findings generated as a result of this project will provide a unifying model linking antioxidant responses as possible factors in regulating cytotoxic reactivities of S and R snail hemocytes. It is responses or generation of reactive oxygen species (ROS), and (3) explore the role of endogenous parasite lectin-like receptors, and if so, whether they are capable of eliciting or inhibiting hemocyte encapsulation known hemocyte lectin-like receptors, (2) determining if schistosome-specific CHOs serve as ligands for hypothesis, research efforts will be directed towards (1) characterizing structural and functional properties of required for effector activity, or relative sensitivities to "anti-immune" parasite mechanisms. To address this oxidative responses) are due either to differences in CHO-recognizing receptors, receptor repertoires, signals differential responses by susceptible (5) and resistant (R) snail cells (e.g., CHO-reactivity, larval adherence, 0 2'U R,< yin 9'm .p-. a); OTC M,.' mm0 non u.ma ,p.,. a"' .0.. Q-- o.- C7K 3 novel approaches to controlling these snail vectors of human disease or the pathogens they carry. .L..